洋地黄通过调控AngⅡ诱导的TGF-β/Smad4通路对慢性心衰伴房颤患者的影响  

Influence of Digitalis on Atrial Fibrillation Associated with Chronic Heart Failure,Mediated Through Regulation of the Angiotensin II-induced TGF-β/Smad4 Pathway

作　　者：苏照海 刘佩 陈辰 段勇 SU Zhaohai;LIU Pei;CHEN Chen;DUAN Yong(Department of Cardiology,Ganzhou Hospital of Guangdong Provincial People's Hospital,Ganzhou Municipal Hospital,Ganzhou,Jiangxi 341099,China;Department of Cardiology,The Third Hospital of Changsha,Changsha,Hunan 410035,China)

机构地区：[1]广东省人民医院赣州医院(赣州市立医院)心血管内科,江西赣州341099 [2]长沙市第三医院心血管内科,湖南长沙410035

出　　处：《今日药学》2025年第1期12-17,共6页Pharmacy Today

基　　金：江西省自然科学基金资助项目(20212BAB216072)。

摘　　要：目的 探讨小剂量洋地黄对慢性心衰(chronic heart failure,CHF)伴心房颤动(atrial fibrillation,AF)患者TGF-β/Smad4信号通路、神经内分泌因子水平及房颤结构重构的影响及可能机制。方法 选取2021年7月~2023年6月某院收治的76例CHF伴AF患者为研究对象。根据治疗方法不同分为联合组(n=38)与对照组(n=38)。两组均行利伐沙班片治疗治疗,联合组加用小剂量洋地黄。对比两组疗效、房颤结构重构指标、外周血TGF-β/Smad4 mRNA表达情况、神经内分泌因子指标、AF复发率、不良反应情况。结果 联合组总有效率(97.37%)高于对照组(81.58%,P <0.05)。两组治疗后LAD、LAVI均低于治疗前(P<0.05),联合组上述房颤结构重构指标均显著低于对照组(P<0.05)。治疗后,两组TGF-β mRNA、Smad4 mRNA、TGF-β/β-actin、Smad4/β-actin低于同组治疗前(P<0.05),且联合组各指标均低于对照组(P<0.05)。两组治疗后神经内分泌因子水平均低于治疗前(P<0.05),联合组神经内分泌因子水平均显著低于对照组(P<0.05)。多元线性回归分析显示,TGF-β、Smad4、ALD、NTproBNP、AngⅡ水平升高是CHF合并AF房颤结构重构的危险因素(P<0.05),而上述指标的下调则是CHF合并AF房颤结构重构改善的影响因素(P<0.05)。不同浓度AngⅡ对CHF伴AF患者PBMC分泌TGF-β mRNA、Smad4 mRNA均有促进作用(P<0.05),且浓度越高生成的TGF-β mRNA、Smad4 mRNA越多(P<0.05)。小剂量洋地黄干预后抑制AngⅡ刺激PBMC合成TGF-β mRNA、Smad4 mRNA。治疗期间,联合组和对照组未见明显不良反应。联合组和对照组AF复发率比较(7.89%vs.10.53%),差异无统计学意义(χ^(2)=0.157,P=0.692)。结论 小剂量洋地黄在改善CHF伴AF患者的房颤结构重构、通过调控AngⅡ来调节TGF-β/Smad4信号通路及神经内分泌因子水平方面表现出显著的疗效和安全性。且房颤结构重构的改善可能与上述指标的表达被抑制有关。OBJECTIVE To investigate the effects of low-dose digitalis on atrial fibrillation(AF) structural remodeling,as well as its potential mechanisms involving the TGF-β/Smad4 signaling pathway and neurohormonal factor levels in patients diagnosed with chronic heart failure(CHF) and concomitant AF.METHODS A total of 76 patients with CHF and AF admitted to The Third Hospital of Changsha from July 2021 to June 2023 were enrolled in this study.Patients were divided into two groups,a combination group(n=38) and a control group(n=38) based on different treatment approaches.Both groups were treated with rivaroxaban tablets,while the combination group additionally received low-dose digitalis.Comparisons were made between the two groups in terms of efficacy,AF structural remodeling indicators,peripheral blood TGF-β/Smad4 mRNA expression,neurohormonal factors,AF recurrence rate,and adverse reactions.RESULTS The total effective rate in the combination group(97.37%) was significantly higher than that in the control group(81.58%,P<0.05).After treatment,both groups showed lower left atrial diameter(LAD) and left atrial volume index(LAVI) compared to before treatment(P<0.05).The combination group exhibited significantly lower values of AF structural remodeling indicators than the control group(P<0.05).Post-treatment levels of TGF-βmRNA,Smad4 mRNA,TGF-β/β-actin,and Smad4/β-actin were significantlylower than pre-treatment levels in both groups(P<0.05),with the combination group showing lower levels of all these indicators compared to the control group(P<0.05),with the combination group showing lower levels than the control group(P<0.05).Both groups also exhibited reduced levels of neurohormonal factors after treatment(P<0.05),with the combination group showing significantly lower levels compared to the control group(P<0.05).Multivariate linear regression analysis revealed that elevated levels of TGF-β,Smad4,ALD,NT-proBNP,and AngⅡwere risk factors for structural remodeling of AF in patients with CHF combined with AF(P<0.05).In

关 键 词：慢性心力衰竭 房颤 小剂量洋地黄 房颤结构重构 TGF-β/Smad4信号通路 神经内分泌因子 

分 类 号：R969[医药卫生—药理学]